The overall objective of this research is to understand the molecular basis for the control of the biosynthesis of parathyroid hormone (PTH). We have recently partially isolated the mRNA for PTH and have translated it in a wheat germ cell free system. The principal protein formed is pre-ProPTH, a presumed precursor to both PTH and its cellular precursor, ProPTH. I plan to isolate PTH mRNA in sufficient quantities so that the biosynthesis, structure and function of the mRNA can be studied. The experimental key to much of this study will be the production of DNA complementary (cDNA) to the purified mRNA. cDNA can be used as a probe in hybridization studies to assay for PTH mRNA or for genetic sequences that correspond to PTH mRNA. It also serves as a template for the production of highly radioactive copies of PTH mRNA necessary for sequence studies. The specific objectives of this proposed research are to: 1) study the structure and function of pre-ProPTH; 2) study the structure, biosynthesis and translation of PTH mRNA; and 3) develop defined cell free systems in which the transcription and translation of the mRNA can be studied.